High risk of diabetes yet healthy – why?

Not all of the children who run an increased risk of developing type 1 diabetes actually develop the disease. Why is this? Researchers at LiU are studying the immune defence in detail, attempting to find out more about the mechanisms behind the disease and possible treatments.

Linda Åkerman prepares an extraction of DNA from cells. Photo credit: Kajsa JuslinWhen the first symptoms of type 1 diabetes appear, the process has already been under way for some time, unnoticed. Even before a person becomes ill, it is often possible to find in their blood antibodies directed against natural substances in their body. These are known as “auto-antibodies”, and their presence is a sign that the immune system has started to destroy the insulin-producing cells in the pancreas. People who have several different diabetes-related auto-antibodies are at an increased risk of developing the disease in the future.

What is really happening during this invisible civil war in the body, before symptoms appear?

Half became ill

ABIS (All Babies in Southeast Sweden) is a large study being carried out under the leadership of Johnny Ludvigsson, in which 17,000 children have been followed from birth. These children have all provided blood samples. Linda Åkerman’s doctoral project at LiU has involved following a group of children from ABIS who ran a higher risk of developing type 1 diabetes. Of the 46 children who had several different auto-antibodies, approximately half developed clinical diabetes before the age of eleven years. Those who were still healthy but were believed to run a higher risk of developing the disease continued to provide blood samples for two years.Linda Åkerman Photo credit: Thor Balkhed

“Some of these children developed type 1 diabetes during the study, while others were diagnosed some time after the follow-up period. Some still haven’t developed the disease, and even if they are at a higher risk for diabetes, we don’t know for sure whether all of them will actually develop the disease,” says Linda Åkerman.

Much of our knowledge about what happens in the period before the disease breaks out comes from studies of people whose relatives have developed type 1 diabetes. Such people are subject to a hereditary risk of developing the disease. However, most people who develop type 1 diabetes do not have a close relative with diabetes, and the mechanisms that lead to such people developing the disease may be different.

“This is why we believe that it is important to study this particular group of children, since they are drawn from the general population in Sweden, rather than being selected due to their family background,” says Linda Åkerman.

The crucial question

The research group noticed that the children who developed diabetes seemed to have higher levels of two auto-antibodies, IA2A and ZnT8A, than children who remained healthy. Other studies have also suggested that these auto-antibodies indicate a particularly high risk for developing diabetes, and the research group believes that it is important to determine whether this is true for risk groups from different populations. Such information may be useful in clinical studies that aim to prevent type 1 diabetes, in order to be able to determine how high the risk is that a participant will develop diabetes.Rosaura Casas wants to know what happens in the body before symptoms of diabetes type 1 arise. Photo credit: Kajsa Juslin

LiU researcher, and one of Linda Åkerman’s PhD supervisors, Rosaura Casas says that it is important to determine why some children with an increased risk actually become ill, while others have still not developed diabetes after ten years, despite having these auto-antibodies in their blood.

“We want to understand what is happening in the body during this period. Is there a time window here when it would be possible to stop the disease developing?”

This is, of course, a crucial question in diabetes research: Is it possible to find a way to stop or reduce the way in which the immune system attacks insulin-producing cells? Several clinical studies are in progress in Sweden, principally in Linköping, in which researchers are testing new treatments for people who have recently developed type 1 diabetes. One such study is the DIAGNODE study. It is hoped that it will be possible in the long term to preserve insulin production before it completely disappears. Rosaura Casas and other members of the research group are investigating blood samples from patients who are participating in several treatment studies. They are particularly interested in different sorts of immune cells, or white blood cells, and how they communicate with each other.Linda Åkerman has followed a group of children with high risk of developing diabetes type 1. Photo credit: Kajsa Juslin

Does one size fit all?

One thing the researchers are looking for are markers that can show at an early stage whether a person is responding to treatment or not. But the research is also attempting to determine whether the effects of treatment are influenced by differences between different patient’s immune systems. Different patients have, for example, different auto-antibodies, and Rosaura Casas believes that these differences are important.

“It has been generally accepted in diabetes research that all patients respond to the treatment being tested. But the immune systems of people who develop diabetes can be very different. The idea is growing that one treatment may not necessarily be appropriate for all patients. I suspect that in the future we will work in the way they do in cancer treatment, where several different treatments are often combined.”

This article has also been published in Forskning & Utveckling 1/2017, a magazine by the Faculty of Medicine and Health Sciences at LiU and Region Östergötland.